Ada R.S. Diehl

Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: A double-blind randomized trial†‡

the study was designed to test whether vitamin E (VE) provides oral mucosal protection in patients with irradiated cancers of the head and neck.

Rapid rescreening of cervical smears for internal quality control

OBJECTIVE To assess the performance of quick rescreening as an internal quality control for cervical smears previously screened as negative and to compare this method with clinically indicated rescreening of negative smears and with further 10% random rescreening. STUDY DESIGN In a small-workload laboratory with many different types of indications for cytology, during a three-month period, all gynecologic cytology smears considered negative for significant findings (anything above atypical squamous cells of undetermined significance (ASCUS)/atypical glandular cells of undetermined significance (AGUS) in the Bethesda System) or inadequate were quickly rescreened using a 10 x objective. RESULTS Of the total 2,188 smears processed, 164 (7.5%) were excluded from rapid review because they were positive on routine screening, and 2,024 cases were subjected to rapid rescreening: 1,925 (95.1%) cases were considered negative and 99 (4.9%) positive for significant findings; 58 of the latter were confirmed and 41 not confirmed by the cytopathologists detailed examination. The 58 confirmed cases were classified as: 43 ASCUS/AGUS, 14 of low grade squamous intraepithelial lesion and 1 of invasive cancer. No cases of high grade squamous intraepithelial lesion were detected. CONCLUSION Considering that the routine screening and internal quality control of the laboratory had detected 117 positive cases, the additional 58 represent a definite increase in the efficiency of a small-workload laboratory. In such a clinical setting, no additional case of a high grade lesion was detected by rapid rescreening. The increase in cost and time was considered very reasonable, and the method was incorporated as quality control for the laboratory. Clinically indicated rescreening of negative smears and random 10% rescreening after random rescreening did not add significantly to quality assurance.

Upper gastrointestinal fiberoptic endoscopy in pediatric patients.

Upper gastrointestinal fiberendoscopy in pediatric patients is done safely and under local anesthesia in most instances. This study of 47 children confirmed the value of fiberendoscopy in establishing the etiology of upper gastrointestinal hemorrhage and the presence of esophageal varices. It also contributed significantly to the management of patients with disphagia, pyrosis, epigastric pain, and ingestion of foreign bodies. No significant morbidity was caused.

Automated Primary Screening Devices

failure might vary widely. During the past year there has been a lull in the previously very active promotion of primary screening devices. It appears that economic projections for the manufacturers did not materialize. This offers a good opportunity to assess the situation and to suggest where the development might go from here. The first question to be raised requires that we return to the beginning. What is the problem that automation of primary screening is to solve? The often-quoted Wall Street Journal article (Bogdanich W: The pap test misses much cervical cancer through lab’s errors. Nov 2, 1987) called attention to several concerns. There were concerns about the reliability of the reading of a Pap smear, about the possibility of shortages in highly trained personnel and about labor costs. The resulting availability of capital for technology development undoubtedly responded to the need to support the control of cervical cancer, but one has to consider that a prime motivation was the potential for economic gain. There is nothing wrong with that notion in principle, but inevitably it had major consequences. The first consequence was that technical solutions to the problem were explored almost entirely with the medical/economic situation in the United States in mind. A device had to process a slide within a very short time frame so that system throughput would meet revenue projections. Device costs were weighed against amortization schemes, projected unit sales and return on investment capital. There were discussions about acceptable false negative rates and how these might be pegged to revised estimates of false negative rates in current laboratory practice. There were serious and justified concerns about the risk of lawsuits in the United States. One cannot help, though, particularly on the ocAfter 35 years of basic research and development, automated screening devices for cervical cancer went into clinical trials and entered clinical practice. The results have been encouraging and might be called a success in several ways. The United States FDA approved two devices; both proved to perform at a level equal to or better than claimed by the manufacturers. Beyond that the field tests established that it should be possible to design systems that might find approval by the cytopathology community. The devices in the clinical trials were, after all, only first-generation designs. There is no complex technology that performs at the level of its potential until several generations of designs have evolved. As first-generation devices, given the very substantial difficulties of the problem and the circumstances under which their development took place, they performed remarkably well. Eliminating design compromises dictated either by the state of technology at the time of development or by the development climate concomitant with venture capital financing would produce the next generation of primary screening systems that come much closer to a performance level well respected by medical professionals. One might hear the argument that since performance of the first-generation devices was critically assessed by the FDA in the United States, why should the profession call for improvements? It is true that the FDA approved these devices. However, one has to understand that the FDA here merely certified that the devices perform at the level claimed by the manufacturer. If one wanted to be unkind, one might suggest that the industry set its own standard. In practice it would essentially be the laboratory director who decides whether a claimed performance level can be maintained and is acceptable or not. The extent to which such a decision would be based on a thorough understanding

Combined carcinoembryonic antigen and cytopathologic examination in ascites.

OBJECTIVE To investigate use of the combined carcinoembryonic antigen (CEA) test and cytopathologic examination to improve the diagnosis of neoplastic vs. nonneoplastic ascites. STUDY DESIGN The tests were performed prospectively on 130 patients with ascites whose effusions were submitted for cytologic examination. RESULTS Sixty-seven patients had epithelial tumors, and the cytologic examination was positive in 39 (58.2%). The CEA level was > or = 11.0 ng/mL in 36 patients (53.73%). CEA was helpful in the diagnosis in 18 cases, increasing to 57 (85.07%) the number of positive diagnoses. Eight samples of nonepithelial tumors had low levels of CEA. In 55 patients with nonneoplasic ascites the cytopathologic examination was negative, but the CEA assay was > 11.0 ng/mL in 3 patients. CONCLUSION The cytopathologic examination should be performed in all cases, and the CEA assay should be done in suspected cases of epithelial neoplasia in which the cytologic examination was negative, there was uncertainty about the histologic type of neoplasia, or a diagnosis of nonepithelial neoplasia was made. When ascitic leukocytosis or hepatic failure is present, one should be cautious in interpreting the CEA assay because false positivity can occur.

Detecting p53 immunoexpression in esophageal mucosa with exfoliative cytology in individuals at risk for squamous cell carcinoma of the esophagus.

OBJECTIVE To determine the prevalence of p53 expression in cytologic smear collected by the RS Balloon in high-risk individuals, and test its yield in the cytologic screening of squamous cell carcinoma of the esophagus (SCCE). STUDY DESIGN Asymptomatic individuals at risk for SCCE underwent esophageal exfoliative cytology with the RS Balloon immediately followed by upper gastrointestinal endoscopy with biopsies of unstained areas after iodine mucosal staining of the esophagus. For each patient, cytologic expression of p53 was compared with the worst endoscopic biopsy diagnosis and the histologic expression of p53. RESULTS One hundred seventy-one individuals were submitted to the studys protocol. There were 8 lost cases (4.7%) due to inadequate cytologic samples. The final sample consisted of 163 individuals where 150 were male (92%), mean age of 52.6 +/- 12.0 years old. There were 3 cases of dysplasia/SCCE. Immunohistochemical expression of p53 protein was positive in 38 patients (23.6%), with basal layer expression in 29 (76.3%), middle layer expression in 8 (21.1%) and superficial layer in 1 (2.6%). All patients with dysplasia/SCCE had positive immunohistochemical expression of p53 protein. Immunocytochemical expression of p53 protein in cytologic smear was negative in all cytology samples. CONCLUSION The negative results of immunocytochemical expression of p53 protein suggest that its use does not contribute to improving the performance of conventional cytology of the esophagus in the screening for SCCE and its precursor lesions.

3534 High grade dysplasias are present in normal appearing esophageal mucosa in subjects at risk for squamous cell carcinoma in southern brazil.

Objectives: Subjects at risk for squamous cell carcinoma of the esophagus were examined for mucosal abnormalities that could contain high grade dysplasias and/or early cancer with upper gastrointestinal endoscopy. Methods: Individuals found with cytology atypias at a screening program using esophageal balloon were submitted to esophagoscopy and the mucosa examined before and after Lugol spraying and biopsies obtained from unstained and stained areas. Results: 1495 subjects were screened and 122 underwent endoscopy. Their mean age was 57,8 and 75 (61.5%) were males. They were exposed, daily, to known risk factors as hot mate infusion drinking (91%), cigarrette smoking (51.6%) and alcohol drinking (19.7%). Conventional esophagoscopy visualized minute mucosal lesions (focal hyperemia, erosion, ulceration, nodule, depression / elevation, white plaque, red focal area) in 78 (63.9%) subjects but it was normal in 44 (36.1%). After Lugol spraying unstained areas were seen in 82 (67.2 %) individuals, 61 of which localized in mucosa with normal appearance with biopsies disclosing 10 dysplasias ( 5 high and 5 low grade) while 21, coincident with visible abnormalities had adenocarcinoma in one and a low grade dysplasia in another. Stained mucosa were also biopsied randomly in all subjects and 2 dysplasias were found (1 high and 1 low grade). Lugol esophagoscopy unstained areas had sensitivity of 83.3%, specificity of 61.1 %, positive predictive value of 6.09% and negative predictive value of 99.1% to detect high grade dysplasias ( p = 0.03, Fishers exact test). All high grade dysplasias were present in normal appearing esophageal mucosa. Conclusions: High grade dysplasias were occult in normal appearing mucosa and most were detected only after addition of Lugol staining to the esophageal mucosa.